A Phase Ⅱ Trial of Pyrotinib Combination With CDK4/6 Inhibitor SHR6390 in Patients Prior Trastuzumab-treated Advanced HER2-Positive Breast Cancer

NCT04095390 | Unknown Phase 2

• 1 other identifier: HR-BLTN-010
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The study is being conducted to evaluate the efficacy, safety and tolerability of pyrotinib combination with CDK4/6 Inhibitor SHR6390 in advanced HER2-Positive breast cancer patients who prior trastuzumab-treated.

Conditions

Metastatic Breast Cancer; HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Overall Response Rate (ORR)

  ORR was defined as percentage of participants with best (confirmed) overall response (BOR) of either CR or PR. ORR was assessed by the investigator according to RECIST version 1.1 and is based on BOR, which is defined as best response recorded from start of study treatment until disease progression/recurrence or death. Participants needed to have two consecutive assessments of PR or CR to be a responder. Only participants with measurable disease at baseline were included in the analysis of BOR and who did not have any evaluable post-baseline assessments were classified as not evaluable. The ORR will be reported by percentage with each arms and appropriate confidence intervals.

  2 months

Secondary Outcomes (5)

• Progression-Free Survival (PFS)

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

• Survival Rate

  12 months

• Clinical Benefit Response (CBR)

  2 months

• Adverse Events (AEs)

  Up to 3 years

Study Arms (3)

Arm A

EXPERIMENTAL

Hormone receptor positive,HER2 positive participants will receive Pyrotinib in combination with CDK4/6 Inhibitor SHR6390 plus Letrozole until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Drug: Pyrotinib; Drug: SHR6390; Drug: Letrozole

Arm B

EXPERIMENTAL

Hormone receptor negative,HER2 positive participants will receive Pyrotinib in combination with CDK4/6 Inhibitor SHR6390 plus Capecitabine until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Drug: Pyrotinib; Drug: SHR6390; Drug: Capecitabine

Arm C

EXPERIMENTAL

Hormone receptor negative,HER2 positive participants will receive Pyrotinib in combination with CDK4/6 Inhibitor SHR6390 until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Drug: Pyrotinib; Drug: SHR6390

Interventions

Pyrotinib DRUG

400 mg

Arm A; Arm B; Arm C

SHR6390 DRUG

125mg

Arm A; Arm B; Arm C

Letrozole DRUG

2.5mg

Arm A

Capecitabine DRUG

500mg

Arm B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic HER2-Positive breast cancer prior trastuzumab-treated;
• Years, female;
• HER2-positive breast cancer(according to 2018 ASCO/CAP HER2 test guideline IHC 3+ or IHC 2+ and FISH, SISH or CISH+);
• Status of hormone receptor is known, Estrogen receptor(ER) or Progesterone receptor(PR) positive is defined as the percentage of cells positive for ER or PR expression ≥ 10%;
• ECOG performance status 0 or 1;
• Life expectancy is not less than 12 weeks;
• At least one measurable lesion according to RECIST 1.1;
• Patients treated with systemic treatment for advanced / metastatic breast cancer≤1 line;
• Natural postmenopausal or OFS in Arm A;
• Adequate function of major organs meets the following requirements (no blood components have been used within 7 days and cell growth factors have been used within 14 days before randomization):
• Neutrophils ≥ 1.5×10\^9/L
• Platelets ≥ 100×10\^9/L
• Hemoglobin ≥ 90g/L
• Total bilirubin≤ 1.5 × the upper limit of normal (ULN)
• ALT and AST ≤ 2.5 × ULN (ALT and AST≤5×ULN if liver metastasis)

You may not qualify if:

• Patients with central nervous system metastasis (Excluding asymptomatic brain metastases or CNS metastases stable by local treatment);
• Unable to swallow, chronic diarrhea and intestinal obstruction, gastrointestinal absorption disorders that interfere with drug absorption;
• Patients who received radiotherapy, chemotherapy, surgery (excluding local puncture) or molecular targeted therapy within 4 weeks before admission; those who received anti-tumor endocrine therapy after screening period;
• Participated in other drug clinical trials within 4 weeks before admission;
• Tyrosine kinase inhibitors targeting HER2 (Neratinib, Lapatinib, pyrotinib, etc.) have been used or are being used in the past;
• Previously received any CDK4/6 inhibitor treatment;
• Previously received Capecitabine in HR- patients;
• Patients with other malignant tumors within 5 years or at the same time( except for cured skin basal cell carcinoma and cervical carcinoma in situ);
• Patients receive any anti-tumor treatments other than the regimen;
• Have a history of allergies to the drug components of this regimen,; history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, history of organ transplantation;
• Have severe heart disease;
• According to the judgement of the researchers, any serious coexisting disease might be harmful to the patient's safety or avoid the patients from accomplishing the treatment(e.g serious hypertension, diabetes, thyroid dysfunction,active infection etc.);
• Female patients during pregnancy and lactation, fertile women with positive baseline pregnancy tests or women of childbearing age who are unwilling to take effective contraceptive measures throughout the trial;
• History of neurological or psychiatric disorders, including epilepsy or dementia;
• Any other situation evaluated by researchers.

Sponsors & Collaborators

• Jinming Yu: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

Study Sites (1)

Breast Cancer Center, Shandong Cancer Hospital Affiliated to Shandong University

Jinan, 250117, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pyrotinib; Letrozole; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Jinming Yu, MD

CONTACT

+8613806406293; jn7984729@public.jn.sd.cn

Yongsheng Wang, MD

CONTACT

+8613505409989; wangysh2008@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Shandong Cancer Hospital and Institute

Study Record Dates

• First Submitted: September 16, 2019
• First Posted: September 19, 2019
• Study Start: September 30, 2019
• Primary Completion: November 30, 2021
• Study Completion: August 30, 2022
• Last Updated: September 19, 2019

Record last verified: 2019-09

Locations

CN (1)